Pancreas I Flashcards
How does acute pancreatitis occur?
Patho physi starts with intracellular activation of enzymes and local and systemic disease results from inflammatory processes and enzyme injury
Describe the morphology of the cells in the pancreas
90% are acinar cells which are protein/enzyme-synthesizers in the pancreas which are secreted as inactive proenzymes in membrane enclosed vesicles to prevent damage to the cells
What is SPNK-1?
An inhibitor produced in the pancreas designed to prevent activation of trypsin from trypsinogen
How are pancreatic enzymes stimulated to be released from acinar cells?
Either via Gs (cAMP) via VIP or Gq (Ca2+) via Ach secondary messengar pathways that promote exocytosis of vesicles in the pancreatic lumen to be circulated to the GI
It is generally accepted that the earliest event in the pathogenesis of acute pancreatitis is what?
the conversion of pancreatic zymogens to their active forms within the acinar cell.
Co-localization of ZG and lysosomes cause enzymes like cothepsin B to activate trypsin from the zymogen granules which then stimulate autodigestion of the acinar cells
How does early activation of pancreatic proteases cause a localized inflammatory response?
Proteases activate complement, causing recruitment for C3a and C5a and thus PMNs and macrophages. These cells then release cytokines such as TNF-a, IL-1, PAF, and NO which produce vascular injury and inflammatory responses
So how do the local effects of acute pancreatitis present clinically?
There will be pancreatic swelling and liquid extravasation due to inflammatory induced swelling as well as local fat necrosis and hemorrhage leading to pain that raidates to the back and N/V
Acute pancreatitis= FAT necrosis
Islets are typically spared until it becomes very severe
Hemorrhage can occur if vessels are digested!
More hemorrhage here and islet destruction
What mainly causes the fat necrosis seen in acute pancreatitis?
lipase production
Obviously if pancreatic enzymes reach circulation, the initial local inflammation caused by acute pancreatitis will become widespread. How is this prevented?
Circulating enzymes, such as a1-antitrypsin, which inactivates proteases, and a-macroglobulin, which binds to circulating trypsin and facilitates monocyte clearance of the complex, prevent systemic spread
What are the signs and mediators of a poorly contained pancreatitis?
fever, malaise, and confusion via TNFa and Il-6 activation
Hypotension via kallikrein activation
DIC and hemorrhage via thrombin activation, and elastase and chymotrypsin activity
hypoxemia via activation of phospholipase A2 which damage surfactant
hypocalcemia from calcium binding to circulating lipids via a fat saponification process
What percentage of pancreatitis events become disseminated?
Only about 20%
Acute pancreatitis
What are the main causes of acute pancreatitis?
gallstones and EtOH
What are the main symptoms of acute pancreatitis?
abdominal pain that radiates to the back, N/V
How is acute pancreatitis diagnosed?
Two of the following Three required:
- abdominal pain, nausea/vomiting
- Notably elevated serum amylase and lipase more than 3x upper limit of normal
- CT imaging showing pancreatic inflammation
How is acute pancreatitis managed/tx?
IV fluids, pain meds, and remove stones if causative
How is trypsin activated?
A Lysine-IlE bond is broken at the N-terminal of trypsinogen
How is trypsin deactivated and what is the basis of hereditary pancreatitis?
Cleavage of a arg-val bond at the C-terminal deactivates trypsin and in hereditary pancreatitis the Arg is replaced by a His which cant be degraded
More on hereditary pancreatitis
AD disorder and the shared feature of most forms is a defect that increases or sustains the activity of trypsin
Genes implicated in hereditary pancreatitis deserve special note: PRSS1 , and CFTR (cystic fibrosis).
What does the gene PRSS1 (7q34) do?
Serine protease 1 (trypsinogen 1)- Cationic trypsin. Gain-of-function mutations prevent self-inactivation of trypsin
How does mutation of CFTR (7q31) cause pancreatitis?
Epithelial anion channel. Loss-of-function mutations alter fluid pressure and limit bicarbonate secretion, leading to inspissation of secreted fluids and duct obstruction
Mutations in CFTR:
- decrease bicarbonate secretion by pancreatic ductal cells
- promoting protein plugging,
- duct obstruction, and
- the development of pancreatitis.
chronic/long-standing bouts of pancreatitis can lead to what?
40% risk of malignancy, due to chronic inflammation
The common dile duct and the main pancreatic duct exit into the duodenum at the ampulla of vater
ERCP- endoscopy retrograde pancreatogram
What factors suggest a gallstone etiology of pancreatitis?
1) Age 50+
2) Female
3) Amylase over 400 Iu/L
4) AST over 100 U/L
5) Alk phos over 300 Iu/L
Gotta get the gallstones out!
NPO= nothing per oral. I.e. dont want to feed these pts. with acute pancreatitis
IVs= many liters of fluids rapidly
What are some lab predictors of poor outcome with pancreatitis?
- Admission Hematocrit > 44% with failure to decrease after 24 hours of IV fluids.
- Admission BUN > 25 mg/dl with an increase after 24 hours of IV fluids.
- C-reactive protein (CRP) > 150 mg/L at 48 hours.
Why would kidney failure be associated with pancreatitis?
because damage to vessel walls can cause edema and hypotension to develop and the kdineys are not perfused as well (hence the need for fluids)
MS= mental status
T or F. A CT scan can differentiate between interstitial and necrotizing pancreatitis
T.
What are the complications of acute pancreatitis?
- Fluid collections
- Pseudocysts
- Fistulas
–ascites
–pleural effusions
•Splenic vein thrombosis
What causes chronic pancreatitis?
What is the main cause of chronic pancreatitis?
chronic alcohol consumption
What are the symptoms of chronic pancreatitis?
chronic abdominal pain and other evidence of pancreatic dysfunction including diabetes and/or steatorrhea
How is chronic pancreatitis diagnosed and tx?
Diagnosis- imaging
Tx: Pain meds, insulin, and enzyme supplements
Alcohol makes protein secretions thicker and cause obstruction and they can also calcify
marked by less inflammation and more fibrosis
the pain is more chronic and probably more like a 5/10 while the pain associated with acute pancreatitis is much more severe
Ducts can also rupture and form pseudocyts that can get large
the fibrotic pancreas causes increased pressure which irritates nerves and causes more inflammation
obstuction of the common bile duct can also cause pain and infection
Can try to ‘rest’ the pancreas with exogenous enzymes but its not that effective
blocking the splanchnic nerves (via alcohol injection) does help with pain
T or F. Fat malabsorption occurs before protein or carbohydrate in chronic pancreatitis
T. it is primarily due to lipase deficiency
How is the fat malabsorption associated with chronic pancreatitis managed?
–reduce dietary fat intake.
– oral enzyme supplementation- pretty effective (contain lipases and proteases).
– acid suppression therapy (acid will degrade any pancreatic acids you have if you are taking them orally)
When does diabetes occur in chronic pancreatitis?
•Only seen in severe disease (>80% of gland destroyed).
What is unique about pancreatitic induced diabetes?
You see loss of the WHOLE islet- leading to loss of both insulin and glucagon, hence difficult to control (brittle)- glucose can get high or low.
Its better to keep glucose higher than lower due to the severity of hypoglycemic events
T or F. Ketoacidosis is rare in chronic pancreatitis induced diabetes
T. Not sure why
